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耐药基因表达与星形细胞瘤的进展。

Drug-resistance gene expression and progression of astrocytic tumors.

机构信息

Department of Neurosurgery, Kitasato Institute Medical Center Hospital, Kitamoto, Saitama, Japan.

出版信息

Brain Tumor Pathol. 2001;18(2):131-7. doi: 10.1007/BF02479426.

DOI:10.1007/BF02479426
PMID:11908869
Abstract

To clarify the influence of biochemotherapy on the progression of astrocytic tumors, the expression of O6-methylguanine DNA-methyltransferase (MGMT) mRNA, as well as of other drug-resistance- and drug-sensitivity-related genes such as multidrug resistance gene 1, multidrug resistance-associated protein, glutathione S-transferase-pi, DNA topoisomerase II, and interferon receptor mRNA, and the interferon regulatory factor (IRF)-1 and -2 ratios in gliomas were investigated by quantitative reverse transcription-polymerase chain reaction (RT-PCR). The mean MGMT/beta2-microglobulin (beta2-MG) ratio for 130 neuroepithelial tumors was 8.2 +/- 17.8. The mean ratio of 45 glioblastomas was significantly higher than that for the other 85 tumors. In contrast, the mean of 26 low-grade gliomas was significantly lower than that of other tumors. The mean IRF-1/IRF-2 ratio of 16 other brain tumors that mainly consisted of medulloblastomas was significantly greater than that of the other 114 tumors. Almost no significant differences were observed between primary and recurrent tumors in the expression of any gene, and before and after therapy with corresponding drugs. The mean MGMT/beta2-MG ratio in primary glioblastomas was significantly higher than that in secondary tumors. These findings suggest that native drug resistance is more important than acquired resistance when glioma therapy is considered.

摘要

为了阐明生物化学疗法对星形细胞瘤进展的影响,通过定量逆转录聚合酶链反应(RT-PCR)研究了 O6-甲基鸟嘌呤 DNA-甲基转移酶(MGMT)mRNA 的表达,以及多药耐药基因 1、多药耐药相关蛋白、谷胱甘肽 S-转移酶-π、DNA 拓扑异构酶 II 和干扰素受体 mRNA 等其他耐药性和药物敏感性相关基因,以及干扰素调节因子(IRF)-1 和 -2 的比例。130 例神经上皮肿瘤的平均 MGMT/β2-微球蛋白(β2-MG)比值为 8.2±17.8。45 例胶质母细胞瘤的平均值明显高于其他 85 例肿瘤。相比之下,26 例低级别胶质瘤的平均值明显低于其他肿瘤。主要由髓母细胞瘤组成的 16 例其他脑肿瘤的平均 IRF-1/IRF-2 比值明显大于其他 114 例肿瘤。在任何基因的表达以及相应药物治疗前后,原发性和复发性肿瘤之间几乎没有观察到显著差异。原发性胶质母细胞瘤的平均 MGMT/β2-MG 比值明显高于继发性肿瘤。这些发现表明,在考虑胶质细胞瘤治疗时,天然耐药性比获得性耐药性更为重要。

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